Genetic studies have shown that inbred mice vary in their susceptibility to intraperitoneally-inoculated street rabies viruses. SJL, CBA, DBA/2 and BALB/c mice are highly resistant, whereas A.SW/Sn nd A/WySn mice are extremely susceptible. Inoculatioin of F1 hybrids and backcross mice indicate resistance is dominant and that susceptibility is inherited as either one or two genes. Clinical disease is markedly different in the resistant strains of mice. less central nervous system involvement ith minor paralysis is present in SJL and CBA mice, whereas DBA/2 and BALB/c mice develop severe illness wth paralysis. All strains of mice inoculated intracerebrally with 10 LD50 of virus die indicating resistance mechanism(s) and the genetic influence are functional prior toviral invasion of the principal target organ. In contrast to the different susceptibilities noted in mouse strains inoculate with street rabies viruses, all strans of mice inoculated intraperitoneally with highly virulent ixed rabies virus die. Characterization of host genetically regulated defense mechanisms(s) and virus virulence factor(s) are in progress.